Overview:
Metastatic recurrence of solid tumors such as breast and ovarian cancers continues to be a major clinical problem. Current therapies for this stage of disease are not very effective and carry significant side-effects. The magnitude of this problem provides strong rationale for studies that may lead to novel lifestyle or therapeutic strategies for the prevention and treatment of metastatic disease. In this regard, several epidemiological studies show that obesity and elevated cholesterol are associated with an increased risk of metastatic relapse.
Our lab is focused on determining how endocrine and metabolic factors influence tumor immunology, and how we can leverage this knowledge to develop novel therapeutics. Our focus is on cholesterol metabolism and homeostasis in myeloid immune cells.
All Publications:
Cholesterol and Myeloid Immune Cells
Cholesterol metabolite promotes breast cancer metastasis and ovarian cancer progression through myeloid immune cells
Cholesterol metabolite reprograms myeloid immune cells to be highly immune suppressive
27-hydroxycholesterol increases secretion of pro-cancer extracellular vesicles from myeloid immune cells by increasing ROS and dysregulating lysosomes , invoking stem-like and mesenchymal states in cancer cells, allowing them to migrate and resist cytotoxic chemotherapies.
NR0B2 suppresses myeloid immune cell inflammasome reducing regulatory T cells, and a new ligand has robust anti-tumor effects in mouse models.
The cholesterol efflux protein, ABCA1, re-educates macrophages towards an anti-tumor phenotype, increasing their ability to infiltrate tumors, reducing their angiogenic potential, decreasing efferocytosis, and increasing their support of cytotoxic T cell expansion and anti-cancer activity.
Recent review paper from our group, describing how regulators of cholesterol homeostasis influence immune cells and cancer.
External Video describing Cholesterol and Cancer
Other Nuclear Receptors and Cancer
TLX has anticancer effects in triple negative breast cancer